Evaluating the ototoxicity of an anti-MRSA peptide KR-12-a2

Chung Man Sung, Hong Chan Kim, Yong Beom Cho, Song Yub Shin, Chul Ho Jang

Methicillin-Resistant Staphylococcus aureus (MRSA) is an emerging problem for the treatment of chronic suppurative otitis media, and also for pediatric tympanostomy tube otorrhea. To date, there are no effective topical antibiotic drugs to treat MRSA otorrhea. In this study, we evaluated the ototoxicity of topical KR-12-a2 solution on the cochlea when it applied topically in the middle ear of guinea pigs. The antimicrobial activity of KR-12-a2 against MRSA strains was examined by using the inhibition zone test. Topical application of KR-12-a2 solution, Gentamicin (GM) and Phosphate Buffered Saline (PBS) were applied in the middle ear of the guinea pigs after inserting ventilation tubes. Ototoxicity was assessed by Auditory Brainstem Evoked Response (ABR) and Scanning Electron Microscope (SEM) examination. KR-12-a2 produced an inhibition zone against MRSA from 6.25 μg. Hearing threshold in the KR-12-a2 and PBS groups were similar to that before ventilation tube insertion. However, the GM group showed elevation of the hearing threshold and there were statistically significant differences compared to the PBS or the KR-12-a2 group. In the SEM findings, the KR-12-a2 group showed intact outer hair cells. However, the GM group showed total loss of outer hair cells. In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. The KR-12-a2 solution can be used as ototopical drops for treating MRSA otorrhea; however, further evaluations, such as the definition of optimal concentration and combination, are necessary.